This proposal focuses on the regulation of preimplantation mouse embryo development by growth factors. The long term objective of this area of developmental biology is the understanding of how cell proliferation and differentiation are controlled by intercellular signaling molecules. The elucidation of these processes and their genetic basis is critical to an understanding of diseases of uncontrolled cell proliferation (i.e., cancer) and abnormalities of developmental (birth defects), as well as being directly applicable to the regulation of human fertility (both contraceptives and techniques of assisted conception). The specific alm of this proposal is to examine the role of the signaling molecule transforming growth factor-alpha (TGF-alpha) and its receptor, the epidermal growth factor receptor (EGFR), in these processes. Experiments using scanning laser confocal microscopy will examine the temporal and spatial pattern of expression of TGF-alpha during preimplantation mouse development, at the level of expression of mRNA by in situ hybridization, and protein by indirect immunofluorescence. The role of the EGFR will be investigated directly by examining embryo development and gene expression at the level of mRNA and protein expression in embryos lacking a functional EGFR gene by use of mRNA differential display and high- resolution two-dimensional gel electrophoresis.